The Effects of Nifedipine on Ventricular Fibrillation Mean Frequency in a Porcine Model of Prolonged Cardiopulmonary Resuscitation Karl H. Stadlbauer, MD, Klaus Rheinberger, MSc, Volker Wenzel, MD, Claus Raedler, MD, Anette C. Krismer, MD, Hans-Ulrich Strohmenger, MD, Sven Augenstein, MD, Horst G. Wagner-Berger, MD, Wolfgang G. Voelckel, MD, Karl H. Lindner, MD, and Anton Amann, PhD Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University, Innsbruck, Austria We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during pro- longed cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety sec- onds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P  0.01) increased in nifedipine versus placebo pigs (mean  sd: 12.4  2.1 Hz versus 8  0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventric- ular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P  0.05) increased in nifedipine versus placebo animals (9.7  1.2 Hz ver- sus 7.1  1.3 Hz). Coronary perfusion pressure was sig- nificantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclu- sion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean fre- quency after the induction of cardiac arrest and main- tained ventricular fibrillation mean frequency at 10 Hz during prolonged CPR; this was nevertheless asso- ciated with no defibrillation success. (Anesth Analg 2003;97:226 –30) I ntracellular Ca 2+ increases promptly with the in- duction of ventricular fibrillation (1). This increase in intracellular Ca 2+ is several times more than the peak systolic intracellular Ca 2+ content during normal sinus rhythm and has important metabolic and me- chanical consequences. For example, a large concen- tration of intracellular Ca 2+ increases activation of enzymes that actively transport Ca 2+ into the sarco- plasmic reticulum and mitochondria (2– 4), resulting in a significant intracellular energy deficit. Accord- ingly, calcium channel blockers may preserve meta- bolic machinery and reduce the production of cerebral catabolites, resulting in prolonged cell viability during global ischemia (5). Although a randomized clinical trial using a cal- cium channel blocker in comatose survivors of cardiac arrest did not reveal beneficial effects of this drug with regard to neurologic outcome during a 6-mo follow- up, it is possible that the treatment effect was simply too small to be detectable in a clinical trial of only 520 cardiac arrest patients (6). Also, the calcium channel blocker was given after the return of spontaneous circulation, which may have limited the protective effects on the cerebrum. Thus, if calcium overload- ing is prevented early, beneficial effects may be more likely; further, if the goal of the treatment strategy is not an extremely difficult target, such as preventing Supported by the Austrian National Bank, Vienna, Austria; the Austrian Heart Foundation Project 98/05, Vienna, Austria; a dean’s grant for medical school graduates of the Leopold-Franzens- University, Innsbruck, Austria; the Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University, Inns- bruck, Austria; and Austrian Science Foundation Grant P14169- MED, Vienna, Austria. No author has a conflict of interest with regard to drugs or devices discussed in this article. Accepted for publication January 23, 2003. Address correspondence and reprint requests to Karl H. Lindner, MD, Leopold-Franzens-University, Department of Anesthesiology and Critical Care Medicine, Anichstrasse 35, 6020 Innsbruck, Aus- tria. Address e-mail to karl-heinz.stadlbauer@uibk.ac.at DOI: 10.1213/01.ANE.0000068801.28430.ED ©2003 by the International Anesthesia Research Society 226 Anesth Analg 2003;97:226–30 0003-2999/03